I don't think tmd on the whole protein will adjust the ligand conformation
unless you use a very high force constant. It's hard to give more advice
without knowing what you want to learn. You can certainly find a way to
force this change, but it becomes increasingly artificial.
On Feb 23, 2016 8:32 AM, "Jean-Marc Billod" <jmbillod.cib.csic.es> wrote:
> Thank you very much for your answer.
> The ring is from uridine hence no symmetric, indeed a flipping of the ring
> would require a temporary increase of the local rmsd which is not
> favourable due to the penalty on the energy, maybe explaining the local
> minimum.
> I also tried performing the tMD starting from the final state of the first
> tMD applying a new tMD constraint just for the ligand, which did not work
> either.
> For the dihedral restraint would you suggest to change nmropt=1 from the
> beginning?
>
>
> > On 23 Feb 2016, at 13:19, Carlos Simmerling <carlos.simmerling.gmail.com>
> wrote:
> >
> > Maybe you need a dihedral restraint? A flipped ring isn't going to show
> up
> > strongly in an entire protein rmsd. Is the ring symmetric? Depending on
> the
> > details, the rmsd may go up as it flips, thus your current structure may
> be
> > a local minimum.
> > On Feb 23, 2016 6:26 AM, "Jean-Marc Billod" <jmbillod.cib.csic.es>
> wrote:
> >
> >> It is indeed what I want and I understand that the ligand isn’t
> >> contributing a lot in the global rmsd average. Is there another way to
> >> force the flipping of the ring?
> >>
> >>> On 23 Feb 2016, at 12:14, Carlos Simmerling <
> carlos.simmerling.gmail.com>
> >> wrote:
> >>>
> >>> Your fit and rmsd mask are for all non water heavy atoms. Is that what
> >> you
> >>> want? If the ligand is a small part of the system it won't contribute
> >> much
> >>> to the average in the rmsd.
> >>> On Feb 23, 2016 4:45 AM, "Jean-Marc Billod" <jmbillod.cib.csic.es>
> >> wrote:
> >>>
> >>>> Dear all,
> >>>>
> >>>> I have performed tMD with AMBER12 using the following script:
> >>>>
> >>>> &cntrl
> >>>> nstlim = 2500000, dt = 0.002,
> >>>> ntx = 1, irest = 0,
> >>>> ntpr = 500, ntwr = 500, ntwx = 500,
> >>>> tempi = 300., temp0 = 300.,
> >>>> cut = 15.0,
> >>>> ntt = 1,
> >>>> ntb = 2, ntp = 1,
> >>>> ntc = 2, ntf = 2,
> >>>> nscm = 0,
> >>>> itgtmd = 1, tgtmdfrc = 0.25,
> >>>> tgtrmsd = 4.9,
> >>>> tgtfitmask="!.H= & !:WAT",
> >>>> tgtrmsmask="!.H= & !:WAT",
> >>>> nmropt=1,
> >>>>
> >>>> /
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=1, istep2=400000,
> >>>> value1 = 4.9, value2 = 4.2,
> >>>> /
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=400001, istep2=800000,
> >>>> value1 = 4.2, value2 = 3.0,
> >>>> /
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=800001, istep2=1200000,
> >>>> value1 = 3.000, value2 = 2.0,
> >>>> /
> >>>>
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=1200001, istep2=1600000,
> >>>> value1 = 2.000, value2 = 1.0,
> >>>> /
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=1600001, istep2=2000000,
> >>>> value1 = 1.0, value2 = 0.0,
> >>>> /
> >>>> &wt
> >>>> TYPE='TGTRMSD', istep1=2000000, istep2=2500000,
> >>>> value1 = 0.0, value2 = 0.0,
> >>>> /
> >>>>
> >>>> I used two crystal structures with the ligand inside the binding
> pocket;
> >>>> in the final crystal, one aromatic ring of the ligand is flipped
> >> compared
> >>>> to the first crystal. I performed the simulation and I had no error
> but
> >> I
> >>>> realized that the ligand does not undergo the flipping... basically
> only
> >>>> the conformation of the protein changes but not the one of the ligand.
> >> In
> >>>> fact, the last RMSD is not 0:
> >>>>
> >>>> R M S F L U C T U A T I O N S
> >>>>
> >>>>
> >>>> NSTEP = 2500000 TIME(PS) = 5025.000 TEMP(K) = 0.88 PRESS =
> >>>> 107.6
> >>>> Etot = 238.4099 EKtot = 123.0485 EPtot =
> >>>> 268.7670
> >>>> BOND = 32.9511 ANGLE = 48.2236 DIHED =
> >>>> 30.4487
> >>>> 1-4 NB = 18.4036 1-4 EEL = 73.6341 VDWAALS =
> >>>> 195.7646
> >>>> EELEC = 272.2557 EHBOND = 0.0000 RESTRAINT =
> >>>> 210.8199
> >>>> EAMBER (non-restraint) = 57.9471
> >>>> EKCMT = 94.1915 VIRIAL = 1587.6094 VOLUME =
> >>>> 717.5546
> >>>> Density =
> >>>> 0.0011
> >>>> Ewald error estimate: 0.4427E-04
> >>>> Current RMSD from reference: 0.972
> >>>> Current target RMSD: 0.000
> >>>>
> >>>>
> >>>> Am I doing anything wrong? Any suggestions?
> >>>>
> >>>> Thanks a lot,
> >>>> Jean-Marc
> >>>> _______________________________________________
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> >>>>
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Received on Tue Feb 23 2016 - 06:30:04 PST
